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N. B. Gusev - One of the best experts on this subject based on the ideXlab platform.
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Small Heat Shock Proteins and Human Neurodegenerative Diseases
Biochemistry (Moscow), 2019Co-Authors: L. K. Muranova, M. V. Sudnitsyna, A. S. Ryzhavskaya, V. M. Shatov, N. B. GusevAbstract:The review discusses the role of small Heat Shock Proteins (sHsps) in human neurodegenerative disorders, such as Charcot-Marie-Tooth disease (CMT), Parkinson’s and Alzheimer’s diseases, and different forms of tauopathies. The effects of CMT-associated mutations in two small Heat Shock Proteins (HspB1 and HspB8) on the protein stability, oligomeric structure, and chaperone-like activity are described. Mutations in HspB1 shift the equilibrium between different protein oligomeric forms, leading to the alterations in its chaperone-like activity and interaction with protein partners, which can induce damage of the cytoskeleton and neuronal death. Mutations in HspB8 affect its interaction with the adapter protein Bag3, as well as the process of autophagy, also resulting in neuronal death. The impact of sHsps on different forms of amyloidosis is discussed. Experimental studies have shown that sHsps interact with monomers or small oligomers of amyloidogenic Proteins, stabilize their structure, prevent their aggregation, and/or promote their specific proteolytic degradation. This effect might be due to the interaction between the β-strands of sHsps and β-strands of target Proteins, which prevents aggregation of the latter. In cooperation with the other Heat Shock Proteins, sHsps can promote disassembly of oligomers formed by amyloidogenic Proteins. Despite significant achievements, further investigations are required for understanding the role of sHsps in protection against various neurodegenerative diseases.
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Methylglyoxal and small Heat Shock Proteins
Biochemistry (Moscow), 2017Co-Authors: M. V. Sudnitsyna, N. B. GusevAbstract:Methylglyoxal is a highly reactive dicarbonyl compound formed during glucose metabolism and able to modify phospholipids, nucleic acids, and Proteins belonging to the so-called dicarbonyl proteome. Small Heat Shock Proteins participating in protection of the cell against different unfavorable conditions can be modified by methylglyoxal. The probability of methylglyoxal modification is increased in the case of distortion of glucose metabolism (diabetes), in the case of utilization of glycolysis as the main source of energy (malignancy), and/or at low rate of modified protein turnover. We have analyzed data on modification of small Heat Shock protein HspB1 in different tumors and under distortion of carbohydrate metabolism. Data on the effect of methylglyoxal modification on stability, chaperone-like activity, and antiapoptotic activity of HspB1 were analyzed. We discuss data on methylglyoxal modifications of lens α-crystallins. The mutual dependence and mutual effects of methylglyoxal modification and other posttranslational modifications of lens crystallins are analyzed. We conclude that although there is no doubt that the small Heat Shock Proteins undergo methylglyoxal modification, the physiological significance of this process remains enigmatic, and new experimental approaches should be developed for understanding how this type of modification affects functioning of small Heat Shock Proteins in the cell.
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Small Heat Shock Proteins and diabetes
Moscow University Biological Sciences Bulletin, 2015Co-Authors: M. V. Sudnitsyna, N. B. GusevAbstract:This review is devoted to the analysis of probable participation of small Heat Shock Proteins in different cellular processes of diabetes. Diabetes causes metabolic stress that is accompanied by change of carbohydrate metabolism, accumulation of products of glycation and glycosylation, modulation of protein kinase activity, modulation of redox state of the cell and increase of reactive oxygen species. All these processes can increase expression of small Heat Shock Proteins. Therefore, diabetes increases the level of small Heat Shock Proteins in the heart and retina and certain brain regions and in the kidney cells. Increase of the level of small Heat Shock Proteins can improve transduction of insulin signal and protect the cell against oxidative stress and apoptosis. Different ways providing increase of the level of small Heat Shock Proteins are analyzed. Different mechanisms of covalent modification of Proteins by carbohydrates and their metabolites are described. Data are presented that indicate that hyperglycemia induces modification of different amino acid residues. This leads to the changes in the structure, chemical crosslinking, and modulation of physiologically important properties of the small Heat Shock Proteins. Further detailed investigation of small Heat Shock Proteins might be important for utilization of these Proteins as a promising potential target for development of new approaches for treatment of different forms of diabetes.
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Heterooligomeric complexes of human small Heat Shock Proteins
Cell Stress and Chaperones, 2012Co-Authors: Evgeny V Mymrikov, Alim S. Seit-nebi, N. B. GusevAbstract:Oligomeric association of human small Heat Shock Proteins HspB1, HspB5, HspB6 and HspB8 was analyzed by means of size-exclusion chromatography, analytical ultracentrifugation and chemical cross-linking. Wild-type HspB1 and Cys mutants of HspB5, HspB6 and HspB8 containing a single Cys residue in position homologous to that of Cys137 of human HspB1 were able to generate heterodimers cross-linked by disulfide bond. Cross-linked heterodimers between HspB1/HspB5, HspB1/HspB6 and HspB5/HspB6 were easily produced upon mixing, whereas formation of any heterodimers with participation of HspB8 was significantly less efficient. The size of heterooligomers formed by HspB1/HspB6 and HspB5/HspB6 was different from the size of the corresponding homooligomers. Disulfide cross-linked homodimers of small Heat Shock Proteins were unable to participate in heterooligomer formation. Thus, monomers can be involved in subunit exchange leading to heterooligomer formation and restriction of flexibility induced by disulfide cross-linking prevents subunit exchange.
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large potentials of small Heat Shock Proteins
Physical Review, 2011Co-Authors: Evgeny V Mymrikov, Alim S Seitnebi, N. B. GusevAbstract:Modern classification of the family of human small Heat Shock Proteins (the so-called HSPB) is presented, and the structure and properties of three members of this family are analyzed in detail. Ub...
Pramod K Srivastava - One of the best experts on this subject based on the ideXlab platform.
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Heat Shock Proteins gp96 and hsp70 activate the release of nitric oxide by apcs
Journal of Immunology, 2002Co-Authors: Naveed Panjwani, Lana Popova, Pramod K SrivastavaAbstract:NO is a cytotoxic and immunomodulatory cytokine produced by macrophages and dendritic cells. We show that stimulation of murine and human macrophages with the Heat Shock Proteins gp96 and hsp70 results in induction of inducible NO synthase and the production of NO. The release of NO by monocytes exposed to hsp60 has been documented previously. Immature, but not mature, dendritic cells respond in the same manner. The activity of Heat Shock Proteins is relatively unaffected by an antagonist of LPS, and is abrogated by Heat denaturation. Macrophages have been shown previously to produce NO in response to stimulation with IFN-γ; stimulation of macrophages with mixtures of IFN-γ and gp96 or hsp70 leads to a synergistic production of NO. The present observations extend the roles of these Heat Shock Proteins in innate immune responses to another potent and highly conserved function of APC.
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interaction of Heat Shock Proteins with peptides and antigen presenting cells chaperoning of the innate and adaptive immune responses
Annual Review of Immunology, 2002Co-Authors: Pramod K SrivastavaAbstract:Heat Shock Proteins are abundant soluble intracellular Proteins, present in all cells. Members of the Heat Shock protein family bind peptides including antigenic peptides generated within cells. Heat Shock Proteins also interact with antigen presenting cells through CD91 and other receptors, eliciting a cascade of events including re-presentation of Heat Shock protein-chaperoned peptides by MHC, translocation of NFκB into the nuclei and maturation of dendritic cells. These consequences point to a key role of Heat Shock Proteins in fundamental immunological phenomena such as activation of antigen presenting cells, indirect presentation (or cross-priming), and chaperoning of peptides during antigen presentation. Heat Shock Proteins appear to have been involved in innate immune responses since the emergence of phagocytes in early multicellular organisms and to have been commandeered for adaptive immune responses with the advent of specificity. These properties of Heat Shock Proteins also allow them to be use...
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cd91 is a common receptor for Heat Shock Proteins gp96 hsp90 hsp70 and calreticulin
Immunity, 2001Co-Authors: Sreyashi Basu, Robert J Binder, Thirumalai Ramalingam, Pramod K SrivastavaAbstract:Complexes of the Heat Shock protein gp96 and antigenic peptides are taken up by antigen-presenting cells and presented by MHC class I molecules. In order to explain the unusual efficiency of this process, the uptake of gp96 had been postulated to occur through a receptor, identified recently as CD91. We show here that complexes of peptides with Heat Shock Proteins hsp90, calreticulin, and hsp70 are also taken up by macrophages and dendritic cells and re-presented by MHC class I molecules. All Heat Shock Proteins utilize the CD91 receptor, even though some of the Proteins have no homology with each other. Postuptake processing of gp96-chaperoned peptides requires proteasomes and the transporters associated with antigen processing, utilizing the classical endogenous antigen presentation pathway.
Evgeny V Mymrikov - One of the best experts on this subject based on the ideXlab platform.
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Heterooligomeric complexes of human small Heat Shock Proteins
Cell Stress and Chaperones, 2012Co-Authors: Evgeny V Mymrikov, Alim S. Seit-nebi, N. B. GusevAbstract:Oligomeric association of human small Heat Shock Proteins HspB1, HspB5, HspB6 and HspB8 was analyzed by means of size-exclusion chromatography, analytical ultracentrifugation and chemical cross-linking. Wild-type HspB1 and Cys mutants of HspB5, HspB6 and HspB8 containing a single Cys residue in position homologous to that of Cys137 of human HspB1 were able to generate heterodimers cross-linked by disulfide bond. Cross-linked heterodimers between HspB1/HspB5, HspB1/HspB6 and HspB5/HspB6 were easily produced upon mixing, whereas formation of any heterodimers with participation of HspB8 was significantly less efficient. The size of heterooligomers formed by HspB1/HspB6 and HspB5/HspB6 was different from the size of the corresponding homooligomers. Disulfide cross-linked homodimers of small Heat Shock Proteins were unable to participate in heterooligomer formation. Thus, monomers can be involved in subunit exchange leading to heterooligomer formation and restriction of flexibility induced by disulfide cross-linking prevents subunit exchange.
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large potentials of small Heat Shock Proteins
Physical Review, 2011Co-Authors: Evgeny V Mymrikov, Alim S Seitnebi, N. B. GusevAbstract:Modern classification of the family of human small Heat Shock Proteins (the so-called HSPB) is presented, and the structure and properties of three members of this family are analyzed in detail. Ub...
Carmen Garrido - One of the best experts on this subject based on the ideXlab platform.
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Small Heat Shock Proteins and Fibrosis
Heat Shock Proteins, 2015Co-Authors: Pierre-simon Bellaye, Olivier Burgy, Julien Colas, Sebastien Causse, Carmen Garrido, Philippe BonniaudAbstract:Small Heat Shock Proteins (sHSP) are involved in many essential cellular mechanisms both in physiologic and pathologic conditions. HSP27 (HSPB1), αB-crystallin (HSPB5) and HSP20 (HSPB6), the most studied members, are stress-inducible chaperones with an anti-aggregation function. They have been shown to inhibit apoptosis by interacting with Proteins involved in programmed cell death such as cytochrome c or caspases, to have anti-oxidant properties and/or to modulate protein homeostasis by participating in the proteasomal degradation of specific Proteins under stress conditions. Heat Shock Proteins accumulate in cancer cells and this overexpression is needed for the cancer cells’ survival. Accordingly, the inhibition of Heat Shock Proteins such as HSP27 is an emerging strategy in cancer therapy (already is in phase II clinical trials). Fibrogenesis and cancer share several properties as both pathologies are characterized by genetic alterations, uncontrolled cell proliferation, altered cell interaction and communication and tissue invasion.
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the small Heat Shock Proteins family the long forgotten chaperones
The International Journal of Biochemistry & Cell Biology, 2012Co-Authors: Carmen Garrido, Catherine Paul, Renaud Seigneuric, Harm H KampingaAbstract:Small Heat Shock Proteins are a rather heterogeneous family of ATP-independent chaperones, some of which have been proven to block protein aggregation and help the cells to survive stressful conditions. Although much less studied than high molecular weight HSPs like HSP70/HSPA or HSP90/HSPC, their implication in physio-pathological processes and human diseases is now well evidenced, as it will be discussed in the different reviews of this special issue. In this mini-review we will just present a general introduction about the small Heat Shock Proteins family. This article is part of a Directed Issue entitled: Small HSPs in physiology and pathology.
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small Heat Shock Proteins hsp27 and αb crystallin cytoprotective and oncogenic functions
Antioxidants & Redox Signaling, 2005Co-Authors: Arnaud Parcellier, Elise Schmitt, M Brunet, Arlette Hammann, Eric Solary, Carmen GarridoAbstract:Heat Shock protein-27 (HSP27) and αB-crystallin are ubiquitous small Heat Shock Proteins whose expression is induced in response to a wide variety of physiological and environmental insults. They allow the cells to survive in otherwise lethal conditions. Various mechanisms have been proposed to account for the cytoprotective functions of these small Heat Shock Proteins. First, these Proteins are powerful molecular chaperones whose main function is to prevent the aggregation of nascent and stress-accumulated misfolded Proteins. Second, they interact directly with various components of the tightly regulated programmed cell death machinery, upstream and downstream of the mitochondrial events. Third, they appear to play a role in the proteasomemediated degradation of selected Proteins. Both HSP27 and αB-crystallin were also proposed to participate in the development of neurodegenerative diseases and malignant tumors in which their overexpression could induce drug resistance. Altogether, these properties sugge...
Wilbert C. Boelens - One of the best experts on this subject based on the ideXlab platform.
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Structural aspects of the human small Heat Shock Proteins related to their functional activities
Cell Stress and Chaperones, 2020Co-Authors: Wilbert C. BoelensAbstract:Small Heat Shock Proteins function as chaperones by binding unfolding substrate Proteins in an ATP-independent manner to keep them in a folding-competent state and to prevent irreversible aggregation. They play crucial roles in diseases that are characterized by protein aggregation, such as neurodegenerative and neuromuscular diseases, but are also involved in cataract, cancer, and congenital disorders. For this reason, these Proteins are interesting therapeutic targets for finding molecules that could affect the chaperone activity or compensate specific mutations. This review will give an overview of the available knowledge on the structural complexity of human small Heat Shock Proteins, which may aid in the search for such therapeutic molecules.